A. Nerve Growth Factor
A multi-component protein of molecular weight .about.130,000 has been isolated from mouse salivary glands, it being particularly concentrated in the glands of male mice, which is commonly referred to as "Nerve Growth Factor." The principal neural activity exhibited by the protein has been its ability to cause an increase in the size of sensory neurons, nerve cells which transmit impulses from sensory receptors to the brain, and in the size of sympathetic neurons, one of the two kinds of neurons which make up the autonomic nervous system which regulates the functional activity of the circulatory system, the glands, smooth muscles and other organs.
NGF as obtained by extraction at neutral pH from mouse salivary glands is known as 7S NGF and is made up of three subunits termed .alpha., .beta., .gamma. subunits. All of the neural activity of 7S NGF is exhibited by the .beta. subunit, a dimer of two identical 118 amino acid peptides bound together by non-covalent forces. This subunit is also referred to as 2.5S NGF. The .alpha.- subunit has no known biological activity. The .gamma.-subunit, however, is an arginine esteropeptidase. The initial genetic product in the synthesis of NGF is a prepro-NGF polypeptide which is cleaved by the .gamma.-subunit. The .gamma.-subunit has also been shown to accelerate wound healing in mice.
Recently, a third NGF component (M. wt. .about.116,000) has been reported to have been isolated from mouse salivary glands and to have shown to exhibit the property of being a plasminogen activator, i.e., it converts plasminogen to plasmin, suggesting its utility in the lysis of blood clots. See European Patent Application "Nerve Growth Factor and Process For Obtaining It" 78300656.2 (Publication No. 0002139Al) filed Nov. 22, 1978, published May 30, 1979.
As indicated above, the neural activity of NGF is exhibited by the .beta.-subunit (hereinafter .beta.NGF). It has been shown to stimulate markedly regenerative resprouting of transected axons of central adrenergic neurons, a property which makes it useful in the repair of damaged axons.